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Is Myopathy Part of Statin Therapy (IMPOSTER-16)

Primary Purpose

Myopathic Conditions

Status
Withdrawn
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
cellulose placebo vs. atorvastatin
Sponsored by
Scripps Health
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Myopathic Conditions focused on measuring rhabdomyolysis,, myositis,, myopathy,, statin side effects,, fatty acid oxidation, Statin induced Muscle toxicity

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Primary doctor's permission Patient understands nature of study and has signed consent Patient is >21 years of age Patient willing to stop statin for up to 12 weeks and remain off CoQ10 for study duration Patient able to perform the strength and functional tests required Patient complains of muscle weakness or aching which he/she or his/her physician feels may be attributable to statin therapy CK < 350 IU Thyroid stimulating hormone (TSH) must be normal Fasting respiratory exchange ratio (RER) > 0.80 off statin for at least 4 weeks Exclusion Criteria: Severe underlying illness including: Cr > 3.0, liver failure, unstable angina, symptomatic valvular heart disease, congestive heart failure, or prior cerebrovascular accident (CVA) preventing exercise testing. History of muscle damage (CK > 350 IU) on statins Underlying musculoskeletal disorder preventing muscle testing History of severe depression Taking doses of other medicines with statin sufficient to cause myopathy including: cyclosporine, erythromycin or other macrolide antibiotics; fluconazole; niacin; fibrates; or > 16 oz. of grapefruit juice daily. Diabetes requiring other than diet therapy Use of thiazolidinediones (TZD's), protease inhibitors or other drugs known to influence RER or fatty acid oxidation. Abnormal thyroid status Inability to maintain constant exercise, dietary, and drug regimen during the 16 weeks required by the study protocol.

Sites / Locations

  • Scripps Mercy Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

1

2

Arm Description

statin administration

Outcomes

Primary Outcome Measures

hip flexion
oxygen consumption and anaerobic threshold
muscle pathology score

Secondary Outcome Measures

ability to identify blinded statin
other aerobic exercise indexes
fatty acid oxidation of myocyte cell cultures

Full Information

First Posted
August 4, 2005
Last Updated
November 21, 2022
Sponsor
Scripps Health
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1. Study Identification

Unique Protocol Identification Number
NCT00127335
Brief Title
Is Myopathy Part of Statin Therapy (IMPOSTER-16)
Official Title
Double Blind, Prospective Randomized, Crossover Study of Patients With Muscle Complaints on Statin Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of funding
Study Start Date
August 2005 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Scripps Health

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
There is a significant proportion of patients complaining of muscle symptoms while on statin therapy who have a measurable difference in muscle strength or endurance and whose muscle biopsies are diagnostic for myopathy.
Detailed Description
This is a double-blinded, randomized, placebo-controlled, crossover trial. Sixty patients who are identified by their physician as having muscle pain or weakness while on statin therapy and in whom creatine kinase (CK) enzyme determinations have been normal will be enrolled voluntarily. All patients will have a percutaneous muscle biopsy prior to enrollment into the trial. These patients will be randomized in a blinded crossover fashion to either standardized statin therapy or placebo in eight week intervals. After eight weeks of drug or placebo the patients will be assessed for signs and symptoms of muscle weakness by: Dynamometry of grip and hip strength An exercise test with exhaled gas analysis Blood tests for cholesterol, creatine kinase, lactate Urine tests for organic acids Following the first eight-week study and testing period, each patient will serve as their own control and they will enter a second eight-week study period. During the second phase they will take the opposite therapy, either drug or placebo, which they have not yet received. Sub-studies will include ten controls who have never previously received statins and ten subjects who have suffered statin-induced rhabdomyolysis. Subjects in these sub-studies will not be exposed to statin therapy and will only undergo limited testing.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myopathic Conditions
Keywords
rhabdomyolysis,, myositis,, myopathy,, statin side effects,, fatty acid oxidation, Statin induced Muscle toxicity

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Placebo Comparator
Arm Title
2
Arm Type
Active Comparator
Arm Description
statin administration
Intervention Type
Drug
Intervention Name(s)
cellulose placebo vs. atorvastatin
Other Intervention Name(s)
atorvastatin
Intervention Description
drug
Primary Outcome Measure Information:
Title
hip flexion
Time Frame
8 weeks
Title
oxygen consumption and anaerobic threshold
Time Frame
8 weeks
Title
muscle pathology score
Time Frame
at entry
Secondary Outcome Measure Information:
Title
ability to identify blinded statin
Time Frame
8 weeks
Title
other aerobic exercise indexes
Time Frame
8 weeks
Title
fatty acid oxidation of myocyte cell cultures
Time Frame
at entry

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Primary doctor's permission Patient understands nature of study and has signed consent Patient is >21 years of age Patient willing to stop statin for up to 12 weeks and remain off CoQ10 for study duration Patient able to perform the strength and functional tests required Patient complains of muscle weakness or aching which he/she or his/her physician feels may be attributable to statin therapy CK < 350 IU Thyroid stimulating hormone (TSH) must be normal Fasting respiratory exchange ratio (RER) > 0.80 off statin for at least 4 weeks Exclusion Criteria: Severe underlying illness including: Cr > 3.0, liver failure, unstable angina, symptomatic valvular heart disease, congestive heart failure, or prior cerebrovascular accident (CVA) preventing exercise testing. History of muscle damage (CK > 350 IU) on statins Underlying musculoskeletal disorder preventing muscle testing History of severe depression Taking doses of other medicines with statin sufficient to cause myopathy including: cyclosporine, erythromycin or other macrolide antibiotics; fluconazole; niacin; fibrates; or > 16 oz. of grapefruit juice daily. Diabetes requiring other than diet therapy Use of thiazolidinediones (TZD's), protease inhibitors or other drugs known to influence RER or fatty acid oxidation. Abnormal thyroid status Inability to maintain constant exercise, dietary, and drug regimen during the 16 weeks required by the study protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul S Phillips, MD
Organizational Affiliation
Scripps Health
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harminder Sikand, PharmD
Organizational Affiliation
Scripps Mercy
Official's Role
Study Director
Facility Information:
Facility Name
Scripps Mercy Hospital
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
15492351
Citation
Phillips PS. Ezetimibe and statin-associated myopathy. Ann Intern Med. 2004 Oct 19;141(8):649. doi: 10.7326/0003-4819-141-8-200410190-00021. No abstract available.
Results Reference
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PubMed Identifier
15488882
Citation
Phillips PS, Phillips CT, Sullivan MJ, Naviaux RK, Haas RH. Statin myotoxicity is associated with changes in the cardiopulmonary function. Atherosclerosis. 2004 Nov;177(1):183-8. doi: 10.1016/j.atherosclerosis.2004.06.014.
Results Reference
background
PubMed Identifier
12353945
Citation
Phillips PS, Haas RH, Bannykh S, Hathaway S, Gray NL, Kimura BJ, Vladutiu GD, England JD; Scripps Mercy Clinical Research Center. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med. 2002 Oct 1;137(7):581-5. doi: 10.7326/0003-4819-137-7-200210010-00009.
Results Reference
background
PubMed Identifier
16651050
Citation
Antons KA, Williams CD, Baker SK, Phillips PS. Clinical perspectives of statin-induced rhabdomyolysis. Am J Med. 2006 May;119(5):400-9. doi: 10.1016/j.amjmed.2006.02.007.
Results Reference
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Is Myopathy Part of Statin Therapy (IMPOSTER-16)

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